JP2013076591A - Microchannel device and method for manufacturing the same - Google Patents
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Abstract
Description
本発明は、液体導入路、液体貯留部および液体排出部を有するマイクロ流路デバイス、及びその製造方法に関する。 The present invention relates to a microchannel device having a liquid introduction path, a liquid storage section, and a liquid discharge section, and a manufacturing method thereof.
近年、化学工業（特に、医薬品、試薬等の製造に係る医薬品工業）では、マイクロミキサーまたはマイクロリアクターと呼ばれる微小容器を用いた新しいマイクロ流路デバイスの開発が進められている。マイクロ流路デバイスには、複数本のマイクロチャネル（マイクロ流路と繋がる微小空間（マイクロキャビティ）が設けられており、マイクロチャネルを通して複数の流体を微小空間に合流することで、複数の流体を混合し、又は混合と共に化学反応を生じさせる。 In recent years, in the chemical industry (particularly, the pharmaceutical industry related to the manufacture of pharmaceuticals, reagents, etc.), development of new microchannel devices using micro containers called micromixers or microreactors has been promoted. A microchannel device has a plurality of microchannels (micro spaces connected to the microchannel (microcavity), and a plurality of fluids are mixed with each other through the microchannels to mix a plurality of fluids. Or cause a chemical reaction with mixing.
このようなマイクロ流路デバイスは、ガラス製のものが主流である。ガラス基板でマイクロ分析チップを作成するためには、たとえば、基板に金属、フォトレジスト樹脂をコートし、マイクロチャネルのパターンを焼いた後にエッチング処理を行う方法がある。しかしガラスは大量生産に向かず非常に高コストであり、樹脂化が望まれている。 Such microchannel devices are mainly made of glass. In order to produce a micro-analysis chip with a glass substrate, for example, there is a method in which a metal or a photoresist resin is coated on the substrate and a microchannel pattern is baked, followed by etching. However, glass is not suitable for mass production and is very expensive, and it is desired to use resin.
樹脂製のバイオチップやマイクロ分析チップは、種々の樹脂を用いて射出成形等の各種の成形方法で製造することが可能であり、効率よく経済的なチップ製造が可能となっていた（特許文献１参照）。 Resin-made biochips and microanalysis chips can be manufactured by various molding methods such as injection molding using various resins, enabling efficient and economical chip manufacturing (Patent Literature). 1).
しかしながら、流路サイズに比べて容量の大きい溶液反応部位を有するマイクロ流路チップにおいては、流路を介して流体を溶液反応部位に流し込むと、液体反応部に気泡が残留することがしばしば発生する。 However, in a microchannel chip having a solution reaction site having a larger capacity than the channel size, bubbles often remain in the liquid reaction part when a fluid is flowed into the solution reaction site via the channel. .
本発明の目的は、射出成形で得られる樹脂基板と電極部を有する樹脂基板をマイクロ流路デバイスとして用いる場合であって、樹脂基板であって、マイクロ流路と反応部である液体貯留部を併せ持ち、該液体貯留部に気泡を生じない、または巻き込まないマイクロ流路デバイスを提供することにある。 An object of the present invention is a case where a resin substrate obtained by injection molding and a resin substrate having an electrode portion are used as a microchannel device, wherein the liquid reservoir is a resin substrate, which is a microchannel and a reaction portion. Another object of the present invention is to provide a microchannel device that can be held together and does not generate or entrain bubbles in the liquid reservoir.
このような目的は、下記（１）〜（７）に記載の本発明により達成される。
（１）液体導入路と、液体貯留部と、液体排出部を有するマイクロ流路デバイスであって、
液体導入路および液体排出部の液体貯留部との接合部が、
液体貯留部の側面の同じ高さにないことを特徴とするマイクロ流路デバイス。
（２）液体貯留部の液体導入路の接合部の位置が、液体排出部と液体貯留部の接合部の高さより低い位置にある（１）記載のマイクロ流路デバイス。
（３）液体貯留部が、円柱、角柱形状である（１）または（２）記載のマイクロ流路デバイス。
（４）前記液体貯留部が親水化されている（１）ないし（３）いずれか１項に記載のマイ
クロ流路デバイス。
（５）液体導入路、および液体排出部が溝構造である（１）ないし（４）いずれか１項に記載のマイクロ流路デバイス。
（６）前記マイクロ流路デバイスが、プラスチック樹脂である（１）ないし（５）いずれか１項に記載のマイクロ流路デバイス。
（７）（１）ないし（６）いずれか１項に記載のマイクロ流路デバイスにおいて、液体導入路と液体貯留部を設けた第一基板と、液体貯留部を設けた第二基板と、液体排出部と液体貯留部を設けた第三基板をどれか一つの基板のＴｇ以上の温度で熱圧着する工程を有するマイクロ流路デバイスの製造方法。
Such an object is achieved by the present invention described in the following (1) to (7).
(1) A microchannel device having a liquid introduction path, a liquid storage section, and a liquid discharge section,
The junction between the liquid introduction path and the liquid storage part of the liquid discharge part is
A microchannel device characterized by not being at the same height on the side surface of the liquid reservoir.
(2) The microchannel device according to (1), wherein the position of the joint part of the liquid introduction path of the liquid storage part is lower than the height of the joint part of the liquid discharge part and the liquid storage part.
(3) The microchannel device according to (1) or (2), wherein the liquid storage portion has a cylindrical or prismatic shape.
(4) The microchannel device according to any one of (1) to (3), wherein the liquid storage section is hydrophilized.
(5) The microchannel device according to any one of (1) to (4), wherein the liquid introduction path and the liquid discharge section are groove structures.
(6) The microchannel device according to any one of (1) to (5), wherein the microchannel device is a plastic resin.
(7) In the microchannel device according to any one of (1) to (6), a first substrate provided with a liquid introduction path and a liquid storage unit, a second substrate provided with a liquid storage unit, and a liquid A method of manufacturing a microchannel device, comprising a step of thermocompression bonding a third substrate provided with a discharge unit and a liquid storage unit at a temperature equal to or higher than Tg of any one of the substrates.
本発明によれば、樹脂基板であって、マイクロ流路と反応部である液体貯留部を併せ持ち、該液体貯留部に気泡を生じない、または巻き込まないマイクロ流路デバイスを提供することができる。 According to the present invention, it is possible to provide a microchannel device which is a resin substrate and has both a microchannel and a liquid storage section as a reaction section, and does not generate or entrain bubbles in the liquid storage section.
以下、本発明のマイクロ流路デバイスの製造方法について説明する。
本発明のマイクロ流路デバイスは、液体導入路と、液体貯留部と、液体排出部を有するを有することを特徴とする。
Hereinafter, the manufacturing method of the microchannel device of the present invention will be described.
The microchannel device of the present invention has a liquid introduction path, a liquid storage section, and a liquid discharge section.
以下、本発明のマイクロ流路デバイスの製造方法について詳細に説明する。 Hereinafter, the manufacturing method of the microchannel device of the present invention will be described in detail.
本発明のマイクロ流路デバイスでは、反応部位である液体貯留部に対して少なくとも１本の液体導入路が接続し、また少なくとも１本の液体排出路が接続しているマイクロ流路チップであって（図１、２）、液体導入路の接続部が、常に液体流出部の接続部より下方に存在することを特徴としている（図３）。 The microchannel device according to the present invention is a microchannel chip in which at least one liquid introduction path is connected to a liquid storage portion that is a reaction site, and at least one liquid discharge path is connected. (FIGS. 1 and 2), the connection part of the liquid introduction path is always present below the connection part of the liquid outflow part (FIG. 3).
本願発明の反応部位である液体貯留部は、液体導入路から流体を供給し、貯留部内に液体を溜め、反応等に用いるためのスペースである。液体貯留部の側面は、液体導入路、および液体排出路の流路方向に直角の断面の断面積に比べ大きくなっていることを特徴としている。従って、液体導入路から流体を導入すると徐々に液体貯留部に流体が溜まる構造となっている。 The liquid storage part, which is the reaction site of the present invention, is a space for supplying fluid from the liquid introduction path, storing the liquid in the storage part, and using it for reactions and the like. The side surface of the liquid reservoir is characterized by being larger than the cross-sectional area of the cross section perpendicular to the flow direction of the liquid introduction path and the liquid discharge path. Therefore, when the fluid is introduced from the liquid introduction path, the fluid is gradually accumulated in the liquid reservoir.
上本発明のマイクロ流路デバイスにおいて、液体貯留部の液体導入路の接合部の位置は、液体排出部と液体貯留部の接合部の高さより低い位置にある必要がある。逆の場合、液体導入路から導入させた流体が液体貯留部を完全に満たす前に液体排出路に到達し、液体排出より上方に存在する気相が排出されないまま残留することになる。こうした場合、液体貯留部内の流体量が一定せず、マイクロ流路デバイス間の反応や、測定値に大きな影響を与える。そのために、液体貯留部の液体導入路の接合部の位置は、液体排出部と液体貯留部の接合部の高さより低い位置にある必要がある。 In the microchannel device of the present invention, the position of the joint portion of the liquid reservoir in the liquid introduction path needs to be lower than the height of the joint portion between the liquid discharge section and the liquid reservoir section. In the opposite case, the fluid introduced from the liquid introduction path reaches the liquid discharge path before completely filling the liquid reservoir, and the gas phase existing above the liquid discharge remains without being discharged. In such a case, the amount of fluid in the liquid reservoir is not constant, which greatly affects the reaction between the microchannel devices and the measured value. Therefore, the position of the junction part of the liquid introduction path of the liquid storage part needs to be in a position lower than the height of the junction part of the liquid discharge part and the liquid storage part.
上記のように液体導入路は液体貯留部の側面に接続する必要があるが、接続部位は液体貯留部側面の下方であることが望ましく、好ましくは液体貯留部側面高さの１／２以下の下方で、さらに好ましくは、側面高さの１／３以下の下方である。あるいは、液体導入部の接続部位は液体貯留部底面部に接していても良い。 As described above, the liquid introduction path needs to be connected to the side surface of the liquid storage unit, but the connection site is desirably below the side surface of the liquid storage unit, and is preferably ½ or less of the side height of the liquid storage unit Below, more preferably below 1/3 of the side surface height. Or the connection site | part of the liquid introduction part may be in contact with the liquid storage part bottom face part.
次に液体排出部の接続部位は、液体貯留部側面の上方であることが望ましく、好ましくは液体貯留部側面高さの１／２以上の上方で、さらに好ましくは、側面高さの２／３以上の上方である。あるいは、液体排出部の接続部位は液体貯留部天井部に接していても良い。 Next, the connection part of the liquid discharge part is desirably above the side surface of the liquid storage part, preferably more than 1/2 of the side surface height of the liquid storage part, and more preferably 2/3 of the side surface height. Above. Or the connection site | part of a liquid discharge part may be in contact with the liquid storage part ceiling part.
液体導入路と液体排出路は、具体的には幅が１，０００μｍ以下で、かつ深さが０．０１〜０．５ｍｍの溝構造であることが好ましい。これにより、微小なサイズでの実験等が可能となる。 Specifically, the liquid introduction path and the liquid discharge path preferably have a groove structure having a width of 1,000 μm or less and a depth of 0.01 to 0.5 mm. As a result, an experiment with a very small size is possible.
一方、液体貯留部の側面は、液体導入路、および液体排出路の流路方向に垂直方法の断面の断面積に比べ大きくなっていることが必要である。具体的には、深さが０．１〜２．００ｍｍであり、直径が１ｍｍ〜１０ｍｍの円柱、最大幅が１ｍｍ〜１０ｍｍの多角柱、又はそれらの組み合わせであることが望ましいが、これらに限定するものではない。 On the other hand, the side surface of the liquid storage section needs to be larger than the cross-sectional area of the cross section of the method perpendicular to the flow direction of the liquid introduction path and the liquid discharge path. Specifically, it is desirable that the depth is 0.1 to 2.00 mm, the diameter is 1 mm to 10 mm, the maximum width is 1 mm to 10 mm, or a combination thereof. Not what you want.
また、本願発明のマイクロ流路デバイスの、液体導入路、液体貯留部ならびに液体排出路は、親水化処理が施されてい理うことが好ましい。親水化処理により、基材と流体の親和性が向上し、それにより基材表面と気体との親和性による気体の残留を排除することが可能となり、さらに目的に合致したマイクロ流路デバイスとなる。基材の流体の親和性は、流体物質の基材との接触角で表すことができ、例えば、水の接触角で４０度以下の接触角であると親和性が高いと言える。 Moreover, it is preferable that the liquid introduction path, the liquid storage part, and the liquid discharge path of the microchannel device of the present invention are subjected to a hydrophilic treatment. Hydrophilic treatment improves the affinity between the base material and the fluid, which makes it possible to eliminate residual gas due to the affinity between the base material surface and the gas, and to achieve a microchannel device that meets the purpose. . The affinity of the fluid of the base material can be expressed by the contact angle of the fluid substance with the base material. For example, it can be said that the affinity is high when the contact angle of water is 40 degrees or less.
このマイクロ流路デバイスはプラスチック樹脂で構成されていることが好ましい。これは複雑な流路構造を構成し易いことと、大量に安価にマイクロ流路デバイスを供給することが可能だからでる。 The microchannel device is preferably made of a plastic resin. This is because it is easy to construct a complicated channel structure and it is possible to supply a large number of microchannel devices at low cost.
マイクロ流路デバイスを構成する樹脂としては、例えば高密度ポリエチレン、低密度ポリエチレン、ポリプロピレン、ポリスチレン、各種環状ポリオレフィン、ポリメチルメタクリレート、ポリノルボルネン、ポリフェニレンオキサイド、ポリエチレンテレフタレート、ポリエチレンナフタレート、ポリカーボネート、ポリアミド、ポリイミド、ポリエステル、半硬化状態のフェノール樹脂、半硬化状態のエポキシ樹脂、テフロン（登録商標）、ポリ塩化ビニリデン、ポリ塩化ビニル等が挙げられる。これらの内、アクリル樹脂、飽和環状ポリオレフィン、ポリメチルメタクリレート、ポリカーボネート、ポリスチレンおよびポリエチレンテレフタレートの中から選ばれる１種以上が好ましい。これにより、マイクロ流路デバイスの透明性を向上することができる。 Examples of the resin constituting the microchannel device include high-density polyethylene, low-density polyethylene, polypropylene, polystyrene, various cyclic polyolefins, polymethyl methacrylate, polynorbornene, polyphenylene oxide, polyethylene terephthalate, polyethylene naphthalate, polycarbonate, polyamide, and polyimide. , Polyester, semi-cured phenol resin, semi-cured epoxy resin, Teflon (registered trademark), polyvinylidene chloride, polyvinyl chloride, and the like. Among these, at least one selected from acrylic resin, saturated cyclic polyolefin, polymethyl methacrylate, polycarbonate, polystyrene, and polyethylene terephthalate is preferable. Thereby, the transparency of a microchannel device can be improved.
マイクロ流路デバイスの外形形状は、ハンドリング、分析しやすい形状であればどのような形状であってもよい。例えば、１０ｍｍ角〜２００ｍｍ角程度の大きさが好ましく、１０ｍｍ角〜１００ｍｍ角がより好ましい。マイクロ流路デバイスの外形形状は、分析手法、分析装置に合わせれば良く、正方形、長方形、円形などの形状が挙げられる。 The external shape of the microchannel device may be any shape as long as it is easy to handle and analyze. For example, a size of about 10 mm square to 200 mm square is preferable, and 10 mm square to 100 mm square is more preferable. The external shape of the microchannel device may be matched to the analysis method and the analysis apparatus, and examples thereof include a square shape, a rectangular shape, and a circular shape.
本発明のマイクロ流路デバイスは、例えば以下の方法で作製することができる。
（１）液体導入路と液体貯留部を設けた第一基板
（２）液体貯留部を設けた第二基板
（３）液体排出部と液体貯留部を設けた第三基板
上記基板のどれか一つの基板のＴｇ以上の温度で熱圧着することでマイクロデバイスを製造することができる。
The microchannel device of the present invention can be produced, for example, by the following method.
(1) A first substrate provided with a liquid introduction path and a liquid storage part (2) A second substrate provided with a liquid storage part (3) A third substrate provided with a liquid discharge part and a liquid storage part
A microdevice can be manufactured by thermocompression bonding at a temperature equal to or higher than the Tg of any one of the substrates.
第一のマイクロ流路デバイスの作製方法としては次の通りである。
（１）液体導入路と液体貯留部を設けた第一基板は、基板上に液体導入路を設けた基板であり、該液体導入路は切削加工してもよいし、金型による成形で作製しても良い。
The manufacturing method of the first microchannel device is as follows.
(1) The first substrate provided with the liquid introduction path and the liquid storage portion is a substrate provided with the liquid introduction path on the substrate, and the liquid introduction path may be cut or formed by molding with a mold. You may do it.
次に（２）液体貯留部を設けた第二基板は、基板上に液体貯留部となる孔を設けた基板であり。該基板の厚みにより Next, (2) the second substrate provided with the liquid storage part is a substrate provided with holes serving as the liquid storage part on the substrate. Depending on the thickness of the substrate
次に（３）液体排出路と液体貯留部を設けた第三基板は、基板上に液体排出路を設けた基板であり、該液体導入路は切削加工してもよいし、金型による成形で作製しても良い。
これらの３つの基板を重ねて接合することでマイクロ流路デバイスを得ることができる。
Next, (3) the third substrate provided with the liquid discharge path and the liquid storage portion is a substrate provided with the liquid discharge path on the substrate, and the liquid introduction path may be cut or molded by a mold. You may produce by.
A microchannel device can be obtained by overlapping and bonding these three substrates.
第二のマイクロ流路デバイスの作製方法としては。
（１）液体導入路と液体貯留部を設けた第一基板
（２）液体排出部と液体貯留部を設けた第二基板
これらの２つの基板を重ねて接合することでマイクロ流路デバイスを得ることができる。
As a manufacturing method of the second microchannel device.
(1) A first substrate provided with a liquid introduction path and a liquid storage part (2) A second substrate provided with a liquid discharge part and a liquid storage part By superimposing and joining these two substrates, a microchannel device is obtained. be able to.
第三のマイクロ流路デバイスの作製方法としては、
（１）液体導入路と液体潮流部を設けた第一基板
（２）液体排出路を設けた第二基板
As a production method of the third microchannel device,
(1) A first substrate provided with a liquid introduction path and a liquid power flow part (2) A second substrate provided with a liquid discharge path
第四のマイクロ流路デバイスの作製方法としては、
（１）液体導入路設けた第一基板
（２）液体排出路と液体潮流部を設けた第二基板
これらの２つの基板を重ねて接合することでマイクロ流路デバイスを得ることができる。また、第三、第四のマイクロ流路デバイスの作製方法において、（１）と（２）の基板の間に、液体貯留部を持つ基板を挿入しても良い。
As a production method of the fourth microchannel device,
(1) A first substrate provided with a liquid introduction path (2) A second substrate provided with a liquid discharge path and a liquid flow portion A microchannel device can be obtained by overlapping and bonding these two substrates. In the third and fourth microchannel device manufacturing methods, a substrate having a liquid reservoir may be inserted between the substrates (1) and (2).
マイクロ流路デバイスにおいて基板を接合する方法としては、例えば熱圧着接合、接着剤接合、超音波接合等が挙げられる。これらの中でも流路形状の安定性の面で熱溶着する方法が好ましい。熱溶着の温度としては、どれか一つの基板のＴｇ以上の温度で熱圧着することが好ましい。 Examples of a method for bonding substrates in a microchannel device include thermocompression bonding, adhesive bonding, and ultrasonic bonding. Among these, the method of heat welding is preferable in terms of the stability of the channel shape. As the temperature for thermal welding, it is preferable to perform thermocompression bonding at a temperature equal to or higher than the Tg of any one of the substrates.
このようにして、本発明の製造方法により、マイクロ流路デバイスを得ることができる。 Thus, a microchannel device can be obtained by the manufacturing method of the present invention.
なお、本発明のマイクロ流路デバイスの製造方法の説明については、上述した流路用溝１本について説明したが、本発明のマイクロ流路デバイスの製造方法は、これに限定されず、例えばＹ字状のような分岐を有する溝等を有する樹脂基板にも適用することができる。 In addition, about the description of the manufacturing method of the microchannel device of this invention, although the one groove | channel for flow paths mentioned above was demonstrated, the manufacturing method of the microchannel device of this invention is not limited to this, For example, Y The present invention can also be applied to a resin substrate having a groove having a branch like a letter shape.
１００ マイクロ流路デバイス
１ 流体導入路
２ 流体潮流部
３ 流体排出路
４ 第一のマイクロ流路デバイスの作製方法における第一基板
５ 第一のマイクロ流路デバイスの作製方法における第二基板
６ 第一のマイクロ流路デバイスの作製方法における第三基板
７ 第二のマイクロ流路デバイスの作製方法における第一基板
８ 第二のマイクロ流路デバイスの作製方法における第二基板
９ 第三のマイクロ流路デバイスの作製方法における第一基板
１０ 第三のマイクロ流路デバイスの作製方法における第二基板
１１ 第四のマイクロ流路デバイスの作製方法における第一基板
１２ 第四のマイクロ流路デバイスの作製方法における第二基板
DESCRIPTION OF SYMBOLS 100 Microchannel device 1 Fluid introduction path 2 Fluid tidal part 3 Fluid discharge path 4 First substrate in first microchannel device fabrication method 5 Second substrate in first microchannel device fabrication method 6 First Third substrate 7 in the method for producing a microchannel device 7 First substrate in a method for producing a second microchannel device 8 Second substrate 9 in a method for producing a second microchannel device 9 Third microchannel device The first substrate 10 in the manufacturing method of the second substrate 11 in the manufacturing method of the third microchannel device The first substrate 12 in the method of manufacturing the fourth microchannel device The first substrate 12 in the method of manufacturing the fourth microchannel device Two substrates
Claims (7)
液体導入路および液体排出部の液体貯留部との接合部が、
液体貯留部の側面の同じ高さにないことを特徴とするマイクロ流路デバイス。 A microchannel device having a liquid introduction path, a liquid storage section, and a liquid discharge section,
The junction between the liquid introduction path and the liquid storage part of the liquid discharge part is
A microchannel device characterized by not being at the same height on the side surface of the liquid reservoir.
マイクロ流路デバイス。 The microchannel device according to any one of claims 1 to 5, wherein the microchannel device is a plastic resin.
The microchannel device according to any one of claims 1 to 6, wherein a first substrate provided with a liquid introduction path and a liquid storage part, a second substrate provided with a liquid storage part, a liquid discharge part, A method for manufacturing a microchannel device, comprising a step of thermocompression bonding a third substrate provided with a liquid storage section at a temperature equal to or higher than Tg of any one substrate.
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